Hypertension or high blood pressure is a common cardiovascular disease. Recently, the prevalence rate of hypertension is increasing constantly. According to the newest diagnostic criteria of the World Health Organization (WHO), the prevalence rate of hypertension is about 18.8% of residents aged above 18 years old in China and there are at least more than 200 million patients with hypertension throughout the country, while the number of people with hypertension is more than 960 million throughout the world. Hypertension can cause significant increase in prevalence and hazard rates of complications such as stroke, coronary heart disease, heart failure, kidney disease, large arterial and peripheral arterial disease, etc. The premature deaths resulting from the hypertension rising are up to 1.5 million people each year in China Patients with hypertension constitute 41% of the total chronic outpatients, which occupies the first place in the country. The medical expenses for hypertension are up to 40 billion yuan each year. Therefore, it is significant to prevent and cure hypertension and control the complications resulting from it.
WHO requires that the patients with hypertension need to constantly take medicines throughout their lifetime. Although there are currently many kinds of anti-hypertension drugs, the prevention and treatment for hypertension, prediction of efficacy, and control of complication and hazard fail to reach the desired requirements. Thus, the task for the prevention and treatment of hypertension is still arduous in our country. Combination therapy is a direction of treating hypertension, which helps to interfere with multiple blood pressure-maintaining mechanisms, eliminate genetic individual differences in response to drugs, add or supplement pharmacological action and neutralize adverse reactions resulting from different drugs, thus reduce the dosages of a single drug and decrease the adverse reactions, so as to better protect the target organs and increase patient compliance. Modern studies have indicated that the combination use of drugs with different mechanism of action can increase the efficiency of the treatment of hypertension to 80-90%, which is higher than the efficiency of the treatment with each of the drugs alone (40-60%). The combination of angiotensin II receptor antagonists (ARBs) (sartans) with diuretics is a common combination of drug compound in clinical treatment. Among the currently common used ARBs, candesartan has significant advantages in antihypertensive efficacy. Research data shows that the inhibitory effect of candesartan on AT1 receptor is the strongest, and the inhibitory effect of candesartan on vasoconstriction caused by angiotensin is also the strongest. Compared with other antihypertensive drugs, candesartan is safer and has more definite effect than calcium antagonist, thiazide diuretic and ACEI. However, candesartan also has disadvantages that its effectiveness is no longer increase when the dosage thereof has been increased to a certain level. Therefore, it is needed to combine candesartan with other antihypertensive drugs to achieve the purpose of effectively lowering the blood pressure in the treatment of many patients.
The diuretic hydrochlorothiazide lowers the blood pressure by enhancing sodium excreting of kidney out of the body. Hydrochlorothiazide may produces synergetic effect with candesartan, and the mechanism is that the diuretic can activate the rennin-angiotensin system (RAS), which makes the change of blood pressure more dependent on RAS, and thus enhancing the antihypertensive effect of candesartan and meanwhile compensating for the disadvantage of activating RAS caused by using hydrochlorothiazide alone. Furthermore, hydrochlorothiazide may also cause hypokalemia when it is used alone, and the dosage of hydrochlorothiazide can be lowered to reduce the occurrence of hypokalemia when it is used in combination with candesartan. Currently, candesartan cilexetil/hydrochlorothiazide compound has already come to the market.
In recent years, the clinical position of the diuretic chlorthalidone is re-recognized. Compared with hydrochlorothiazide, chlorthalidone has longer half-life, which results in an enduring antihypertensive effect, especially chlorthalidonein the night. Clinical studies show that chlorthalidone 12.5-25 mg/d of chlorthalidone and 25-50 mg/d of hydrochlorothiazide lower 24-hour blood pressure by 12.4 and 7.4 mmHg respectively, and lower the night-time blood pressure by 13.5 and 6.4 mmHg respectively. It can be seen that chlorthalidone has a greater advantage in antihypertensive effect. Khoska believes that the effect of chlorthalidone on reducing the systolic blood pressure (SBP) is better than that of hydrochlorothiazide, as the antihypertensive efficacy of chlorthalidone is about 1.5-2 times of that of hydrochlorothiazide, and chlorthalidone has a longer action time. Thus, when blood pressure control is not ideal, chlorthalidone, rather than hydrochlorothiazide, should be first used. Clinical studies indicate that the valid control rates of blood pressure of chlorthalidone, amlodipine and lisinopril are 68.2%, 66.3% and 61.2% respectively. Chlorthalidone is better than amlodipine in the prevention of heart failure, and is better than lisinopril in the prevention of stroke. The clinical study on the compound composed of azilsartan and chlorthalidone has been performed. The results of the study on this compound in 1714 patients show that the compound of “azilsartan+chlorthalidone” is better than the compound of “olmesartan+hydrochlorothiazide” in the effect of reducing SBP, and the compound of “azilsartan+chlorthalidone” can reduce the SBP by 22.9-29.8 mmHg compared with the basic value, whereas single azilsartan reduces the SBP by 12.1-15.9 mmHg compared with the basic value and single chlorthalidone reduces the SBP by 12.7-15.9 mmHg compared with the basic value. Thus, it can be seen that the compound of azilsartan+chlorthalidone has a greater advantage.